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Osteoporotic fracture (OF) is associated with high disability and morbidity rates. The burden of OF may be reduced by early identification of subjects who are vulnerable to fracture. Although the current fracture risk assessment model includes clinical risk factors (CRFs) and bone mineral density (BMD), its overall ability to identify individuals at high risk for fracture remains suboptimal. Efforts have therefore been made to identify potential biomarkers that can predict the risk of OF, independent of or combined with CRFs and BMD. This review highlights the emerging biomarkers of bone metabolism, including sphongosine-1-phosphate, leucine-rich repeat-containing 17, macrophage migration inhibitory factor, sclerostin, receptor activator of nuclear factor-κB ligand, and periostin, and the importance of biomarker risk score, generated by combining these markers, in enhancing the accuracy of fracture prediction.
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Type 2 diabetes (T2D) is associated with an increased risk of fracture, which has been reported in several epidemiological studies. However, bone mineral density in T2D is increased and underestimates the fracture risk. Common risk factors for fracture do not fully explain the increased fracture risk observed in patients with T2D. We propose that the pathogenesis of increased fracture risk in T2D is due to low bone turnover caused by osteocyte dysfunction resulting in bone microcracks and fractures. Increased levels of sclerostin may mediate the low bone turnover and may be a novel marker of increased fracture risk, although further research is needed. An impaired incretin response in T2D may also affect bone turnover. Accumulation of advanced glycosylation endproducts may also impair bone strength. Concerning antidiabetic medication, the glitazones are detrimental to bone health and associated with increased fracture risk, and the sulphonylureas may increase fracture risk by causing hypoglycemia. So far, the results on the effect of other antidiabetics are ambiguous. No specific guideline for the management of bone disease in T2D is available and current evidence on the effects of antiosteoporotic medication in T2D is sparse. The aim of this review is to collate current evidence of the pathogenesis, detection and treatment of diabetic bone disease.
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Secondary osteoporosis resulting from specific clinical disorders may be potentially reversible, and thus continuous efforts to find and adequately treat the secondary causes of skeletal fragility are critical to ameliorate fracture risk and to avoid unnecessary treatment with anti-osteoporotic drugs. Among the hyperfunctional adrenal masses, Cushing's syndrome, pheochromocytoma, and primary aldosteronism are receiving particularly great attention due to their high morbidity and mortality mainly by increasing cardiovascular risk. Interestingly, there is accumulating experimental and clinical evidence that adrenal hormones may have direct detrimental effects on bone metabolism as well. Thus, the present review discusses the possibility of adrenal disorders, especially focusing on pheochromocytoma and primary aldosteronism, as secondary causes of osteoporosis.
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Osteoporosis in men is markedly underdiagnosed and undertreated despite higher morbidity and mortality associated with fractures. This study aimed to characterize adult Filipino men with osteopenia, osteoporosis and prevalent fractures.
A cross-sectional study of 184 Filipino men ≥50 years screened for bone mineral density was performed. Age, weight, body mass index (BMI), Osteoporosis Self-Assessment Tool for Asians (OSTA) score, smoking status, family history of fracture, diabetes mellitus, physical inactivity, and T-score were considered.
Of the 184 patients, 40.2% and 29.9% have osteopenia and osteoporosis. Sixteen (21.6%) and 18 (32.1%) osteopenic and osteoporotic men have fragility hip, spine, or forearm fractures. Men aged 50 to 69 years have the same risk of osteoporosis and fractures as those ≥70 years. While hip fractures are higher in osteoporotic men, vertebral fractures are increased in both osteopenic and osteoporotic men. Mere osteopenia predicts the presence of prevalent fractures. A high risk OSTA score can predict fracture. A BMI <21 kg/m2 (
A significant fraction of Filipino men with osteopenia and osteoporosis have prevalent fractures. Our data suggest that fractures occur in men <70 years even before osteoporosis sets in. Low BMI, high OSTA score, and smoking are significant risk factors of osteoporosis.
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Significant improvements in dual-energy X-ray absorptiometry (DXA) concerning quality, image resolution and image acquisition time have allowed the development of various functions. DXA can evaluate bone quality by indirect analysis of micro- and macro-architecture of the bone, which and improve the prediction of fracture risk. DXA can also detect existing fractures, such as vertebral fractures or atypical femur fractures, without additional radiologic imaging and radiation exposure. Moreover, it can assess the metabolic status by the measurement of body composition parameters like muscle mass and visceral fat. Although more studies are required to validate and clinically use these parameters, it is clear that DXA is not just for bone mineral densitometry.
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Vertebral fractures and trabecular bone loss have dominated thinking and research into the pathogenesis and the structural basis of bone fragility during the last 70 years. However, 80% of all fractures are non-vertebral and occur at regions assembled using large amounts of cortical bone; only 20% of fractures are vertebral. Moreover, ~80% of the skeleton is cortical and ~70% of all bone loss is cortical even though trabecular bone is lost more rapidly than cortical bone. Bone is lost because remodelling becomes unbalanced after midlife. Most cortical bone loss occurs by intracortical, not endocortical remodelling. Each remodelling event removes more bone than deposited enlarging existing canals which eventually coalesce eroding and thinning the cortex from 'within.' Thus, there is a need to study the decay of cortical as well as trabecular bone, and to develop drugs that restore the strength of both types of bone. It is now possible to accurately quantify cortical porosity and trabecular decay
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The association between calcium supplementation and adverse cardiovascular events has recently become a topic of debate due to the publication of two epidemiological studies and one meta-analysis of randomized controlled clinical trials. The reports indicate that there is a significant increase in adverse cardiovascular events following supplementation with calcium; however, a number of experts have raised several issues with these reports such as inconsistencies in attempts to reproduce the findings in other populations and questions concerning the validity of the data due to low compliance, biases in case ascertainment, and/or a lack of adjustment. Additionally, the Auckland Calcium Study, the Women's Health Initiative, and many other studies included in the meta-analysis obtained data from calcium-replete subjects and it is not clear whether the same risk profile would be observed in populations with low calcium intakes. Dietary calcium intake varies widely throughout the world and it is especially low in East Asia, although the risk of cardiovascular events is less prominent in this region. Therefore, clarification is necessary regarding the occurrence of adverse cardiovascular events following calcium supplementation and whether this relationship can be generalized to populations with low calcium intakes. Additionally, the skeletal benefits from calcium supplementation are greater in subjects with low calcium intakes and, therefore, the risk-benefit ratio of calcium supplementation is likely to differ based on the dietary calcium intake and risks of osteoporosis and cardiovascular diseases of various populations. Further studies investigating the risk-benefit profiles of calcium supplementation in various populations are required to develop population-specific guidelines for individuals of different genders, ages, ethnicities, and risk profiles around the world.
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Denosumab, a fully human recombinant monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL), blocks binding of RANKL to the RANK receptor, found on the surface of osteoclasts and osteoclast precursors, resulting in decreased bone resorption. Subcutaneous denosumab administration once every 6 months increases bone mineral density at the lumbar spine, total hip, and/or femoral neck, and reduces markers of bone turnover significantly in postmenopausal women with osteoporosis. Relative to placebo, denosumab treatment reduces the risk of vertebral, nonvertebral, and hip fractures significantly. The benefits of denosumab treatment are generally obvious after the first dose and were continued for up to 8 years of treatment in an extension study. The tolerability profile of denosumab during this extension phase was consistent with that observed during the initial 3-year FREEDOM trial. Postmarketing safety surveillance has not shown any unexpected findings. Ongoing safety surveillance will more fully define the long-term safety of denosumab. The benefits of denosumab would seem to be greater than its risks. Denosumab is an important choice in the treatment of postmenopausal women with osteoporosis at increased risk of fractures, including older patients who have difficulty with oral bisphosphonate intake and patients who are intolerant of, or unresponsive to, other therapies.
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Several epidemiologic studies suggested that osteoporosis and osteoporotic fractures are not uncommon in South Korea. However, these previous cohort studies had limitations that may have influenced their results and the generalizability of the study conclusions, including small sample sizes, inclusion of only women, enrollment of participants from specific areas, and nonrandom selection of participants. Recently, epidemiologic studies using a nationwide claim register have been performed to overcome these limitations through collaboration between the Korean Society of Bone and Mineral Research and Health Insurance Review Assessments. Our review of the Korean Nationwide-database Osteoporosis Study could be helpful to obtain accurate incidence and prevalence estimations of osteoporosis and osteoporosis-related fractures in Korea.
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